title: Control of uterine microenvironment by foxp3(+) cells facilitates embryo implantation.
abstract: Implantation of the fertilized egg into the maternal uterus depends on the fine balance between inflammatory and anti-inflammatory processes. Whilst regulatory T cells (Tregs) are reportedly involved in protection of allogeneic fetuses against rejection by the maternal immune system, their role for pregnancy to establish, e.g., blastocyst implantation, is not clear. By using 2-photon imaging we show that Foxp3(+) cells accumulated in the mouse uterus during the receptive phase of the estrus cycle. Seminal fluid further fostered Treg expansion. Depletion of Tregs in two Foxp3.DTR-based models prior to pairing drastically impaired implantation and resulted in infiltration of activated T effector cells as well as in uterine inflammation and fibrosis in both allogeneic and syngeneic mating combinations. Genetic deletion of the homing receptor CCR7 interfered with accumulation of Tregs in the uterus and implantation indicating that homing of Tregs to the uterus was mediated by CCR7. Our results demonstrate that Tregs play a critical role in embryo implantation by preventing the development of a hostile uterine microenvironment.
authors.affiliation: Experimental Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University Magdeburg , Magdeburg , Germany ; PDBEB, Center for Neuroscience and Cell Biology, University of Coimbra , Coimbra , Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Teles
authors.forename: Anne
authors.initials: A
authors.lastname: Schumacher
authors.forename: Marie-Cristine
authors.initials: MC
authors.lastname: Kühnle
authors.forename: Nadja
authors.initials: N
authors.lastname: Linzke
authors.forename: Catharina
authors.initials: C
authors.lastname: Thuere
authors.forename: Peter
authors.initials: P
authors.lastname: Reichardt
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Tadokoro
authors.forename: Günter J
authors.initials: GJ
authors.lastname: Hämmerling
authors.forename: Ana Claudia
authors.initials: AC
authors.lastname: Zenclussen
keywords: fibrosis; implantation; inflammation; pregnancy; regulatory T cells